The data base for our current high-resolution structure of the inhibitor complex of the Staphylococcal nuclease is in the process of being improved and extended. Independent analysis of the crystals of the uninhibited enzyme is approaching a second high-resolution structure. The active site is being delineated by the use of phosphonate analogues of di- and trinucleotides. Methylguanidinium ion complexes of simple phosphate esters are under examination both structurally and kinetically as potentially useful model systems for the enzymatic activity of the nuclease.